This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1002/bit.27600. This article is protected by copyright. All rights reserved. Accepted Article Ali Doryab ORCID iD: 0000-0002-5976-5361 Arti Ahluwalia ORCID iD: 0000-0001-5370-6750 Development of a dynamic in vitro stretch model of the alveolar interface with aerosol delivery Daniele Cei 1,2,3,i , Ali Doryab 3,4,i , Anke-Gabriele Lenz 3,4 , Andreas Schröppel 3,4 , Paula Mayer 3,4 , Gerald Burgstaller 3,4 , Roberta Nossa 1,2 , Arti Ahluwalia ,1, 2,i , Otmar Schmid 3,4,i 1 Research Center “E. Piaggio”, University of Pisa, Largo Lucio Lazzarino 2, 56126 Pisa, Italy 2 Department of Information Engineering, University of Pisa, via Caruso 2, 56126 Pisa, Italy 3 Comprehensive Pneumology Center, Member of the German Center for Lung Research (DZL), Max- Lebsche-Platz 31, 81377 Munich, Germany 4 Institute of Lung Biology and Disease, Helmholtz Zentrum Muenchen, Ingolstaedter Landstrasse 1, D- 85764 Neuherberg, Germany We describe the engineering design, computational modelling and empirical performance of a Moving Air-Liquid Interface (MALI) bioreactor for the study of aerosol deposition on cells cultured on an elastic, porous membrane which mimics both air-liquid interface exposure conditions and mechanoelastic motion of lung tissue during breathing. The device consists of two chambers separated by a cell layer cultured on a porous, flexible membrane. The lower (basolateral) chamber is perfused with cell culture medium simulating blood circulation. The upper (apical) chamber representing the air compartment of the lung is interfaced to an aerosol generator and a pressure actuation system. By cycling the pressure in the apical chamber between 0 and 7 kPa, the membrane can mimic the periodic mechanical strain of the alveolar wall. Focusing on the engineering aspects of the system, we show that membrane strain can be monitored by measuring changes in pressure resulting from the movement of media in the basolateral chamber. Moreover, liquid aerosol deposition at a high dose delivery rate (>1 µl cm -2 min -1 ) is highly efficient